Altered intrinsic hippocmapus declarative memory network and its association with impulsivity in abstinent heroin dependent subjects.

Converging evidence suggests that addiction can be considered a disease of aberrant learning and memory with impulsive decision-making. In the past decades, numerous studies have demonstrated that drug addiction is involved in multiple memory systems such as classical conditioned drug memory, instrumental learning memory and the habitual learning memory. However, most of these studies have focused on the contributions of non-declarative memory, and declarative memory has largely been neglected in the research of addiction. Based on a recent finding that hippocampus, as a core functioning region of declarative memory, was proved biased the decision-making process based on past experiences by spreading associated reward values throughout memory. Our present study focused on the hippocampus. By utilizing seed-based network analysis on the resting-state functional MRI datasets with the seed hippocampus we tested how the intrinsic hippocampal memory network altered toward drug addiction, and examined how the functional connectivity strength within the altered hippocampal network correlated with behavioral index 'impulsivity'. Our results demonstrated that HD group showed enhanced coherence between hippocampus which represents declarative memory system and non-declarative reward-guided learning memory system, and also showed attenuated intrinsic functional link between hippocampus and top-down control system, compared to the CN group. This alteration was furthered found to have behavioral significance over the behavioral index 'impulsivity' measured with Barratt Impulsiveness Scale (BIS). These results provide insights into the mechanism of declarative memory underlying the impulsive behavior in drug addiction.

Dynamic neural responses to cue-reactivity paradigms in heroin-dependent users: an fMRI study.

Neuroimaging methods have been employed to study cue-reactivity-induced neural correlates in the human brain. However, very few studies have focused on characterizing the dynamic neural responses to the factorial interactions between the cues and the subjects. Fifteen right-handed heroin-dependent subjects and 12 age-matched nondrug using subjects participated in this study. Cue-reactivity paradigms were employed, while changes in blood oxygenation level-dependent (BOLD) signals were acquired by functional MRI (fMRI). The fMRI datasets were analyzed with AFNI software and repeated two-way ANOVA was employed for factorial analyses. Neural correlates of factorial interactions between cue-factor and subject-factor were identified in the regions of the ventral tegmental area (VTA), the left and right amygdala, the left and right fusiform cortex, and the precuneus in the mesocorticolimbic system, and in the superior frontal, dorsal lateral prefrontal, and orbitofrontal cortices in the prefrontal cortex system. The neural response patterns in the prefrontal systems are dynamic: decreased response to neutral-cues and increased response to heroin-cues. Further, heroin-cue-induced neural responses within the subregions in the PFC system are significantly intercorrelated. In conclusion, the cue-reactivity paradigms significantly activated the dynamic neural activations in the prefrontal system. It is suggested that the dynamic response patterns in the PFC system characterize the impaired brain control functions in heroin-dependent subjects.

Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study.

AIM: Drug addiction is a chronic brain disease with constant relapse requiring long-term treatment. New pharmacological strategies focus on the development of an effective antirelapse drug. This study examines the effects of levotetrahydropalmatine (l-THP) on reducing heroin craving and increasing the abstinence rate among heroin-dependent patients. METHODS: In total, 120 heroin-dependent patients participated in the randomized, double-blinded, and placebocontrolled study using l-THP treatment. The participants remained in a ward during a 4-week period of l-THP treatment, followed by 4 weeks of observation after treatment. The patients were followed for 3 months after discharge. Outcome measures are the measured severity of the protracted abstinence withdrawal syndrome (PAWS) and the abstinence rate. RESULTS: Four weeks of l-THP treatment significantly ameliorated the severity of PAWS, specifically, somatic syndrome, mood states, insomnia, and drug craving, in comparison to the placebo group. Based on the 3 month follow-up observation, participants who survived the initial 2 weeks of l-THP medication and remained in the trial program had a significantly higher abstinence rate of 47.8% (95% confidence interval [CI]: 33%- 67%) than the 15.2% in the placebo group (95% CI: 7%-25%), according to a log- rank test (P<0.0005). CONCLUSION: l-THP significantly ameliorated PAWS, especially reducing drug craving. Furthermore, it increased the abstinence rate among heroin users. These results support the potential use of l-THP for the treatment of heroin addiction.